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N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial.

ABSTRACT: The acute phase of the nonthyroidal illness syndrome (NTIS) is characterized by low T3 and high rT3 levels, affecting up to 75% of critically ill patients. Oxidative stress has been implicated as a causative factor of the disturbed peripheral thyroid hormone metabolism.The objective of the study was to investigate whether N-acetylcysteine (NAC), a potent intracellular antioxidant, can prevent NTIS in patients with acute myocardial infarction.This was a randomized, multicenter clinical trial.Consecutive patients admitted to the emergency and intensive care units of two tertiary hospitals in southern Brazil were recruited. Patients and intervention included 67 patients were randomized to receive NAC or placebo during 48 hours. Baseline characteristics and blood samples for thyroid hormones and oxidative parameters were collected.Variation of serum T3 and rT3 levels was measured.Baseline characteristics were similar between groups (all P > .05). T3 levels decreased in the placebo group at 12 hours of follow-up (P = .002) but not in NAC-treated patients (P = .10). Baseline rT3 levels were elevated in both groups and decreased over the initial 48 hours in the NAC-treated patients (P = .003) but not in the control group (P = .75). The free T4 and TSH levels were virtually identical between the groups throughout the study period (P > .05). Measurement of total antioxidant status and total carbonyl content demonstrated that oxidative balance was deranged in acute myocardial infarction patients, whereas NAC corrected these alterations (P < .001).NAC administration prevents the derangement in thyroid hormone concentrations commonly occurring in the acute phase of acute myocardial infarction, indicating that oxidative stress is involved in the NTIS pathophysiology.

SUBMITTER: Vidart J

PROVIDER: S-EPMC4255112 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial.

Vidart Josi J Wajner Simone Magagnin SM Leite Rogério Sarmento RS Manica André A Schaan Beatriz D BD Larsen P Reed PR Maia Ana Luiza AL

The Journal of clinical endocrinology and metabolism 20141201 12

<h4>Context</h4>The acute phase of the nonthyroidal illness syndrome (NTIS) is characterized by low T3 and high rT3 levels, affecting up to 75% of critically ill patients. Oxidative stress has been implicated as a causative factor of the disturbed peripheral thyroid hormone metabolism.<h4>Objective</h4>The objective of the study was to investigate whether N-acetylcysteine (NAC), a potent intracellular antioxidant, can prevent NTIS in patients with acute myocardial infarction.<h4>Design</h4>This ...[more]

PMID: 25148231

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Project description:BACKGROUND:Both nonthyroidal illness syndrome and renal dysfunction are associated with increased mortality risk in acute myocardial infarction (AMI). However, it is unclear whether combined NTIS and renal dysfunction further increase mortality risk. Therefore, our aim is to investigate whether combined NTIS and renal dysfunction further increases mortality risk in patients with acute myocardial infarction (AMI). METHODS:A total of 1295 inpatients with AMI were divided into normal group (n?=?692), NTIS group (n?=?139), renal dysfunction group (n?=?304), and combined NTIS and renal dysfunction group (n?=?160). Heart function, in-hospital, all-cause and cardiovascular mortality were compared among the four groups. RESULTS:After adjustment for age and sex, left ventricular ejection fraction was significantly lower in the combined group (48?±?11%) than in the NTIS group (52?±?10%, P?=?0.017), the renal dysfunction group (52?±?10%, P?=?0.001) and the normal group (56?±?8%, P?<?0.001). After controlling for confounding factors, compared with the normal group, the NTIS and the renal dysfunction group represented higher risks of in-hospital mortality (OR: 3.643, P?=?0.028; OR:3.135, P?=?0.042, respectively), all-cause mortality (HR: 2.138, P?=?0.007; HR: 2.050, P?=?0.003, respectively), and cardiovascular mortality (HR:2.134, P?=?0.042; HR:2.237, P?=?0.010, respectively). Compared to those in the NTIS and the renal dysfunction group, the patients in the combined group showed a further increased risk for in-hospital mortality (OR:2.916, P?=?0.039; OR:2.487, P?=?0.036, respectively), all-cause mortality (HR: 1.939, P?=?0.015; HR: 2.020, P?=?0.002, respectively) and cardiovascular mortality (HR:2.420, P?=?0.010; HR:2.303, P?=?0.002, respectively). CONCLUSIONS:Both NTIS and renal dysfunction increase short-term in-hospital mortality, and long-term all-cause and cardiovascular mortality risk in patients with AMI. Furthermore, the coexistence of NTIS and renal dysfunction presents further increased mortality risk in AMI patients.

Project description:Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (?30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.

Project description:BACKGROUND:Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial. METHODS AND OUTCOMES:The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6-8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6-8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6-8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6-8 days and six months. FUNDING, ETHICS AND REGULATORY APPROVALS: This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26). TRIAL REGISTRATION:ClinicalTrials.gov: NCT01388504 and Current Controlled Trials: ISRCTN57596739.

Project description:BackgroundGiven the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly).ObjectivesThis study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial.MethodsThe trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life-5 Dimensions-5 Level visual analogue scale at 12 weeks.ResultsMACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes).ConclusionsYoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408).

Dataset Information

N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial.

Publications

N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial.

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